Insulin-like growth factor-binding protein 2 (IGFBP2), a circulating and locally expressed regulatory protein, has emerged as a context-dependent modulator of metabolic homeostasis with potential relevance to obesity, insulin resistance, type 2 diabetes mellitus (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD). This evidence concerns the gene IGFBP2 and obesity due to melanocortin 4 receptor deficiency.