PNPLA5 is a triacylglycerol lipase belonging to the patatin-like phospholipase domain family with critical roles in lipid metabolism and cellular homeostasis. The protein localizes to lipid droplets through a C-terminal targeting motif containing conserved basic residues 1, where it hydrolyzes triglycerides to mobilize neutral lipids. Beyond lipolysis, PNPLA5 functions in autophagy regulation; the enzyme is required for efficient autophagosome biogenesis by mobilizing lipid droplet-derived lipids to support formation of autophagic membranes 2. This activity is essential for diverse autophagic processes including mitochondrial quality control and microbial clearance. Clinically, rare and low-frequency coding variants in PNPLA5 are significantly associated with altered LDL-cholesterol levels, with effect sizes substantially larger than common variants identified through genome-wide association studies 3. PNPLA5 is being evaluated as a potential diagnostic target for familial hypercholesterolemia cases of unknown genetic etiology 4. However, genetic variation in PNPLA5 does not strongly contribute to childhood obesity 5. These findings establish PNPLA5 as a functionally important lipase with potential relevance to dyslipidemia and cardiovascular risk.