In this context, this review summarizes the structural characteristics and molecular mechanisms of ALKBH5 and discusses its emerging roles across a spectrum of metabolic diseases, including MAFLD, metabolic complications such as diabetic retinopathy (DR), diabetes-associated cognitive impairment (DACI), atherosclerosis (AS), and diabetic cardiomyopathy (DCM), as well as metabolism-related inflammatory diseases represented by rheumatoid arthritis (RA). Here, ALKBH5 is linked to familial dilated cardiomyopathy.