In this study, we investigated the hypothesis that ARAP1 can aggravate ECM accumulation and renal dysfunction and glomerulosclerosis in diabetic db/db mice as well as in GMCs exposed to high glucose through aberrant glycolysis, associated with HIF-1α accumulation led by increased PKM dimer formation as well as decreased PKM tetramer formation through maintaining the EGFR persistent activation. Here, EGFR is linked to glomerulosclerosis.