Cathepsin S has been associated with the pathogenesis of many conditions including but not limited to lung diseases (62), autoimmune diseases (56, 57, 63, 64), CVD (36, 65), type 2 diabetes (66, 67), obesity (58, 68), metabolic syndrome (55), neurodegenerative disease (69), and cancer (70, 71). Here, CTSS is linked to obesity due to melanocortin 4 receptor deficiency.