Act Like It's incompatibility has been resolved! No guarantees every mod that uses Act Like It will work in tandem with a Downfall run, but the baseline issue of 'can't open the boss room' has been fixed.

cannot play gungeon act- failed to select any floor

Replay The Spire's issues have been resolved! Removing it from the incompatibility list.

In a run with wandering minibosses, the miniboss may show up in a merchant fight. When the merchant flees, the battle ends before the miniboss leaves. Then after leaving the shop the game crashes.

Report: Gaining the "Virtuous Blindfold" relic from the Hubris mod hides everything on the map except the bottom row when starting a new zone. In downfall mode, this results in being unable to pick a starting room since the starting rooms are on the top row of the map.

Originally posted by billy_bao:

this results in being unable to pick a starting room since the starting rooms are on the top row of the map.

Just as a minor correction (as I've had this same issue), you should still be able to pick a starting room, however you'll need to try to click on a starting room while unable to see it. If encountering this issue, and you don't want to start over, click around in the dark near the top, and you should be able to get into a room.
Edit: Misspoke, click around near the top of the map, not in the dark. Rooms can't spawn off of the actual map. Click where rooms could naturally spawn and you should be able to access one, though.

can we also get a list of known mods that do work in combination with downfall?

When using SuperFastMode at above 500% speed none of the select 1 of N cards work (like slimebound's default split card and the advance/retract/nothing card of hexaghost)

Lowering it to 500% does make them work as a workaround.

I played the standard run with the Boss character and i ran into some problem could this be a mod compatibility issue ? (i had Lobotomy, Hubris, Minty Spire, some character class plus Infinite Spire).

And i can't select the Heart as a boss even after beating the Spire Spear and Heart.

Found a specific issue that crashed the game with the Wandering Minibosses mod, where one of the Minibosses killed the shopkeeper during a Downfall run.

I had a crash during a merchant fight where a wandering miniboss joined. The merchant died, and then it crashed right after. I happened to have debug logs on: https://gist.github.com/Daenyth/bd9caa8279e6c6e2d84e9f675bbab6ce

Originally posted by billy_bao:

Report: Gaining the "Virtuous Blindfold" relic from the Hubris mod hides everything on the map except the bottom row when starting a new zone. In downfall mode, this results in being unable to pick a starting room since the starting rooms are on the top row of the map.

You actually can pick a room, you just can't see it. I encountered the same issue but by randomly clicking around was able to pick a starting room - still an issue that needs fixing though!

Using Deca's Protection as the Problem Sleuth crashes the game. I had this happen twice, once with 0 of all stats and once with 10 Pulchritude and a few points of the others. I assume it's because it's trying to select a power which I'm capable of playing, and can't find one.

02:10:43.353 ERROR core.CardCrawlGame> Exception caught
java.lang.IllegalArgumentException: n must be positive
at com.badlogic.gdx.math.RandomXS128.nextLong(RandomXS128.java:110) ~[desktop-1.0.jar:?]
at com.badlogic.gdx.math.RandomXS128.nextInt(RandomXS128.java:99) ~[desktop-1.0.jar:?]
at com.megacrit.cardcrawl.random.Random.random(Random.java:65) ~[desktop-1.0.jar:?]
at com.megacrit.cardcrawl.dungeons.AbstractDungeon.returnTrulyRandomCardInCombat(AbstractDungeon.java:1229) ~[?:?]
at expansioncontent.cards.DecasProtection.use(DecasProtection.java:32) ~[downfall.jar:?]
at com.megacrit.cardcrawl.characters.AbstractPlayer.useCard(AbstractPlayer.java:1693) ~[?:?]
at com.megacrit.cardcrawl.actions.GameActionManager.getNextAction(GameActionManager.java:358) ~[?:?]
at com.megacrit.cardcrawl.actions.GameActionManager.update(GameActionManager.java:175) ~[?:?]
at com.megacrit.cardcrawl.rooms.AbstractRoom.update(AbstractRoom.java:325) ~[?:?]
at com.megacrit.cardcrawl.dungeons.AbstractDungeon.update(AbstractDungeon.java:2524) ~[?:?]
at com.megacrit.cardcrawl.core.CardCrawlGame.update(CardCrawlGame.java:881) ~[?:?]
at com.megacrit.cardcrawl.core.CardCrawlGame.render(CardCrawlGame.java:429) [?:?]
at com.badlogic.gdx.backends.lwjgl.LwjglApplication.mainLoop(LwjglApplication.java:225) [?:?]
at com.badlogic.gdx.backends.lwjgl.LwjglApplication$1.run(LwjglApplication.java:126) [desktop-1.0.jar:?]

Using Corrupt Core on a target with no orb slots (via the Lobotomy Corp mod) freezes the game.

Fighting the Merchant when a Wandering Miniboss shows up (in this case Immortal Flame), then having the Merchant flee while the Miniboss is still alive, crashes the game.