My gaming group for the first 5e campaign I ran, I welcomed having a mix of LGBTI players and characters. In the end we had myself (a gay man) as GM, my partner as a pan-sexual Dragonborn bard, a non-binary aasimar warlock played by a lesbian friend, and pretty much everyone else was unspecified or assumed to be cis-gendered, straight and/or asexual (played by cisgendered individuals, one of whom identifies as asexual). As the setting was my own homebrew world, I made sure that there was no issue with gender and sexual diversity (at least in the areas the players visited). I also included same-sex couples among my NPCs, and hopefully not in a way that appeared gratuitous or tokenistic. Those players who did not want to use their character's sexuality in their role-playing were in no way compelled or expected to do so - it was always player choice. As a GM, having a non-binary character was actually a great learning experience in how to manage my use of pronouns. I know I didn't always get it right, but I hope my efforts to be respectful were well received.
In another (non-5e) campaign where I'm a player, I'm playing a female troll. However due to the setting, trolls are very rare and so people don't have much experience in dealing with them. For this reason, my character has been assumed to be male based purely on physicality. However I recently revealed (in-game) my character's actual gender, and there was no issue (with the players at least - in-game consequences are yet to be determined).
Regarding characters with a disability, I haven't had any experience with that scenario in 5e, and I think previous responses as to how to accommodate them within existing mechanics are quite good. Alternatively, if you're interested in homebrewing something, you might want to look to another RPG system for inspiration: Pathfinder. This system has/had an interesting class called the Oracle. These characters are Clerics that are analogous to the Sorcerer, in that their powers are given to them somewhat unwillingly; this power always comes with a "curse". However these curses also come with benefits which grow as the character's power grows. For example, an Oracle with the Clouded Vision curse can't see beyond 30ft, but within that range they have Darkvision (if not already granted by their race). At higher levels, this darkvision increases, eventually becoming Blindsight out to 15ft (the ability to sense without sight, including bypassing invisibility!), and these effects are cumulative. As another example, a "Lame"-cursed Oracle has reduced movement, but is unaffected by encumbrance, eventually becoming immune to fatigue and exhaustion. The downside of the Oracle is that the modelling of the disability is based on the chosen class, not the character. But it might give you some inspiration on how to model physical disabilities without necessarily penalizing the player.
Best of luck!
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My gaming group for the first 5e campaign I ran, I welcomed having a mix of LGBTI players and characters. In the end we had myself (a gay man) as GM, my partner as a pan-sexual Dragonborn bard, a non-binary aasimar warlock played by a lesbian friend, and pretty much everyone else was unspecified or assumed to be cis-gendered, straight and/or asexual (played by cisgendered individuals, one of whom identifies as asexual). As the setting was my own homebrew world, I made sure that there was no issue with gender and sexual diversity (at least in the areas the players visited). I also included same-sex couples among my NPCs, and hopefully not in a way that appeared gratuitous or tokenistic. Those players who did not want to use their character's sexuality in their role-playing were in no way compelled or expected to do so - it was always player choice. As a GM, having a non-binary character was actually a great learning experience in how to manage my use of pronouns. I know I didn't always get it right, but I hope my efforts to be respectful were well received.
In another (non-5e) campaign where I'm a player, I'm playing a female troll. However due to the setting, trolls are very rare and so people don't have much experience in dealing with them. For this reason, my character has been assumed to be male based purely on physicality. However I recently revealed (in-game) my character's actual gender, and there was no issue (with the players at least - in-game consequences are yet to be determined).
Regarding characters with a disability, I haven't had any experience with that scenario in 5e, and I think previous responses as to how to accommodate them within existing mechanics are quite good. Alternatively, if you're interested in homebrewing something, you might want to look to another RPG system for inspiration: Pathfinder. This system has/had an interesting class called the Oracle. These characters are Clerics that are analogous to the Sorcerer, in that their powers are given to them somewhat unwillingly; this power always comes with a "curse". However these curses also come with benefits which grow as the character's power grows. For example, an Oracle with the Clouded Vision curse can't see beyond 30ft, but within that range they have Darkvision (if not already granted by their race). At higher levels, this darkvision increases, eventually becoming Blindsight out to 15ft (the ability to sense without sight, including bypassing invisibility!), and these effects are cumulative. As another example, a "Lame"-cursed Oracle has reduced movement, but is unaffected by encumbrance, eventually becoming immune to fatigue and exhaustion. The downside of the Oracle is that the modelling of the disability is based on the chosen class, not the character. But it might give you some inspiration on how to model physical disabilities without necessarily penalizing the player.
Best of luck!