Considering the homology between MACC1 and SH3BP4, and the function of SH3BP4 in regulating endocytosis and receptor signaling in cancer cells, we hypothesize a role of MACC1 in clathrin-mediated endocytosis (CME) and investigated its effect on iron accumulation and receptor tyrosine kinase (RTK) signaling, and thus promoting CRC cell proliferation and metastasis. The gene discussed is SH3BP4; the disease is colorectal carcinoma.