PLEKHM1 (pleckstrin homology and RUN domain containing M1) functions as a critical adaptor protein that facilitates autophagosome-lysosome fusion during autophagy 1. The protein promotes this fusion process by mediating the association between GABARAP family proteins and other autophagy machinery components, thereby enabling autophagic clearance of protein aggregates 1. PLEKHM1 localizes to lysosomes and plays a role in late endosome to lysosome transport and lysosome positioning 2. During respiratory syncytial virus infection, PLEKHM1 is recruited to cholesterol-rich lysosomes along with HOPS VPS39 to facilitate minus-end transport of autophagosomes and autolysosome formation 3. The protein has been implicated in sleep regulation, specifically daytime napping behavior 4. Disease-wise, mutations in PLEKHM1 cause autosomal recessive and dominant forms of osteopetrosis, a bone disorder characterized by defective bone resorption [disease associations noted]. Additionally, PLEKHM1 variants have been associated with progressive supranuclear palsy, a neurodegenerative disease, where functional regulatory variants disrupt transcriptional networks 5. The protein's role in autophagosome-lysosome fusion makes it essential for cellular homeostasis and proper clearance of cellular debris.