I have a machine with an approx 1000mm long gantry, driven at each end. Couple of ways in which it can get out of square:

One motor stalls for some reason, or sometimes when I hit the e-stop button. If the two motors do not stop at the same time, or come to a halt at slightly different rates, you have lost sync.

When you first power on the stepper drivers, the motors may or may not be at a full-step point. If not, it's likely that the driver will initialize it to the nearest full step, although I believe that some drivers are supposed to remember the last state when powered down. It's possible that if this happens often enough, the gantry may drift slowly out of square, a tiny amount each power-down/power-up cycle.

Homing both ends to a known position gets round these problems; on my machine it will hold these settings for an entire session unless one of the above happens.