Studies (Ando et al., 2013; Hattersley et al., 2021; Ravikumar et al., 2010) reveal abnormal cleavage of PICALM in AD brains, with significantly reduced 75 kDa PICALM levels, disrupted cathepsin D (Cath D) processing, and impaired lysosomal function, leading to autophagy deficits and inhibited Tau degradation. The gene discussed is PICALM; the disease is Alzheimer disease.