At lysosomes with minor membrane damage, Ca2+is released and recruits the ESCRT machinery including IST1. If damage increases, SPG20 detects lipid-packing defects and binds IST1. SPG20 recruits and activates ITCH that ubiquitylates membrane-associated proteins to initiate lysophagy. Damage detection by SPG20 does not require permeability of the membrane for proteins.
