what lock on does
Lock on hands your aiming to the game. Once a target is chosen, every attack goes toward it regardless of where the cursor or the aiming stick points, which separates your movement from your aim completely. It works on enemies, bosses and critters alike.
Where you get it depends on platform. Console, mobile and the 3DS version have it running permanently. On desktop it turns itself on once a supported controller is connected and stays out of the way otherwise.
picking and changing targets
The lock on button grabs the most appropriate nearby target. Pressing it again either moves to the next candidate or drops the lock, depending on what is around you. A held target gets three yellow arrows around it, and if it leaves the screen the display changes to two arrows pointing after it, which is genuinely useful against anything that circles wide before coming back.
the priority setting
Lock On Priority decides which enemy gets picked when several are in range, and the two options behave very differently in a crowd. Clearest Line takes the enemy nearest your cursor that you have an unobstructed view of, so walls and platforms rule targets out. Target Closest ignores geometry and takes whatever is physically nearest, including something standing behind a block. Clearest Line is the better default when you are fighting through terrain. Target Closest suits an open arena, where the nearest thing is usually the thing about to hit you.
what it refuses to hold
- Invincible enemies cannot be targeted at all, and neither can town NPCs or other players.
- A lock often breaks the moment its target goes briefly invincible or loses its hitbox, which is exactly what happens with anything that teleports.
- Enemy caster projectiles can be targeted, which is occasionally the right call when you would rather delete the spell than the caster.
when it wins and when it costs you damage
The strongest case is a small screen and awkward aim. On handheld the visible area is tight enough that manual aiming is a real handicap, and lock on removes it. Yoyos, ranged weapons and magic all benefit, and strafing becomes free, since you can spend your whole attention on dodging while shots keep landing.
The weakness is that it aims at where the target was the instant you fired, not where it is going. Against anything fast or small, or with any weapon whose projectiles travel slowly, a large share of your shots pass behind the enemy. Manual aim wins those matchups outright, and dropping the lock is better than fighting it.
One place it is clearly better: in the second phase of an Expert Brain of Cthulhu fight, lock on goes for the real brain rather than the illusions, which takes the entire puzzle out of that phase.