MC3R is a G protein-coupled receptor that binds melanocyte-stimulating hormones (α-, β-, and γ-MSH) and ACTH, coupling to Gs protein to activate adenylate cyclase and cAMP-dependent signaling. Beyond its classical role in energy homeostasis, MC3R regulates growth, pubertal timing, and circadian rhythms—processes that depend on nutritional availability. Loss-of-function mutations in MC3R associate with delayed puberty, reduced linear growth, and decreased lean mass 1, with recent evidence suggesting MC3R amplifies signaling in the context of puberty timing 2. In the liver, MC3R activation promotes lipid droplet autophagy and lipid metabolism; global mc3r knockout mice develop obesity with hepatic triglyceride accumulation and impaired hepatocellular autophagy 3. Two common missense variants (Thr6Lys and Val81Ile) show evidence of association with childhood obesity under a recessive inheritance model 4, though the pathogenic role remains debated 5. MC3R agonists, including modimelanotide, represent a therapeutic avenue for obesity and metabolic disease, offering a mechanistically distinct approach from MC4R-targeted agents.