Apart from classical proteins related with lipolysis, such as adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), carboxylesterase 2 (CES2) is recently discovered as an efficient diglyceride, monoglyceride, and triglyceride hydrolase, which plays a causal role in the development of obesity and fatty liver diseases in human and murine (Li et al., 2016; Chalhoub et al., 2021). The gene discussed is PNPLA2; the disease is obesity due to melanocortin 4 receptor deficiency.