But, 2 RIR or failure? Does it make a difference to gains? Cause it sure makes a difference going to failure vs two reps left.
The literature suggests that going to failure vs. leaving 0-2 RIR is roughly similar in terms of hypertrophy. The literature also suggests that humans are terrible at assessing RIR.
Think of it like this, as the muscle fatigues, more muscle fibers are recruited up to the point of maximal neuromuscular recruitment, which is peak mechanical tension on the muscle fibers and that's roughly what stimulates hypertrophy. Prior to that point there's very little hypertrophic signaling.
So, we can conclude that getting close to failure is critical and that going to actual momentary muscular failure can cause more fatigue and extend recovery times, which is problematic if one is trying to hit 20+ sets per week and each successive set per workout yields diminishing returns in terms of growth.
This is where "science" lets us down. It doesn't know how well we recover or sleep or how genetically gifted we are in terms of muscle growth. I can, for example hit my lats once a week and they grow like crazy. Same for quads. I try to hit 20 sets a week for my pecs and they're still lackluster.
In any case, if you can truly get to 2 RIR, then you'll be fine. If you get it wrong, you won't see optimal gains. This is where exercise selection and training modification can come into play. I think Nippard said this above and it's something I commonly do, which is go to 1-2RIR for my work sets and take the last set to failure. I also pick exercises that are easy to fail on. A barbell bench, for example is not something you want to fail without a spotter, but a chest press machine is fine. Failing a squat is usually a dramatic moment in any gym, but a leg press, not so much.
If you look at how the pros train, they tend to push the intensity, fail often, and even do forced reps to guarantee they're getting the most gains.
Speaking of failing a squat, it's story time:
When I was 16 I was in a strength training program in high school with a coach that was wildly irresponsible in that there was a lot of ego lifting. I failed a four plate squat after getting 3 reps. Rather than spot me, the coach kinda pulled me out from under the bar and I dumped it forward onto one of those L-shaped squat racks that bounced forward into a giant mirror because it wasn't bolted down. The mirror exploded of course. It was pretty wild.