Model of CASM activation. (1) Stimuli that induce perturbations in endolysosomal ion and pH balance drive (2) V0–V1 engagement that (3) promotes the recruitment of ATG16L1 through its WD40 CTD and results in CASM. SopF modifies V-ATPase to inhibit ATG16L1 interaction while BafA1and ConA interfere with V-ATPase activity, both resulting in inhibition of CASM. During LAP, NOX2-dependent ROS production consumes phagosomal H⁺ protons in a DPI and GSK sensitive manner, which alters phagosome pH and drives the SopF-sensitive interaction between V-ATPase and ATG16L1, which then directs ATG8 lipidation to phagosomes.