It has been shown that p31comet can inhibit INSR endocytosis by inhibiting the interaction of BUBR1 and INSR-bound MAD2, and liver-specific p31comet−/− mice exhibit reduced INSR levels and develop systemic insulin resistance, while Bubr1 deficiency delays INSR endocytosis and improves insulin sensitivity in mice29,44. The gene discussed is INS; the disease is Insulin resistance.