Cytosolic lipid storage droplets are primary functional organelles that regulate 
cellular lipid metabolism and homeostasis. Paradoxically, excess lipid stores 
are linked to both adaptive (fasting and chronic exercise) and mal-adaptive 
(obesity and related health complications) conditions. Thus, collective 
metabolic and physiological processes must balance lipid storage and utilization 
with prevention of lipocytotoxicity and compounding tissue dysfunctions, urging 
the need to further define the connection of mammalian lipid droplet function 
and lipid homeostasis. The perilipins are a multi-protein family that targets 
lipid droplet surfaces and regulates lipid storage and hydrolysis. Study of 
perilipin functions has provided insight into the physiological roles of 
cytosolic lipid droplets and their relationship with obesity-related 
pathologies. Here, we review the current knowledge of the multiple perilipin 
proteins in regulating tissue-specific lipid droplets and associations with 
tissue and systemic energetics.