As summarized in this review, our laboratory has demonstrated in the last couple of decades that loss in hepatic CEACAM1 expression and its defective phosphorylation impair insulin clearance and subsequently, play a pivotal role in insulin resistance, fatty liver disease, and obesity (Figure 1) (9, 10, 16–19, 25, 27, 39, 53, 60, 61). The gene discussed is CEACAM1; the disease is obesity due to melanocortin 4 receptor deficiency.