Nmrk2, also known as nicotinamide ribokinase 2 or muscle integrin binding protein (MIBP), is involved in nicotinamide adenine dinucleotde (NAD) coenzyme biosynthesis [1,4]. It phosphorylates the nicotinamide riboside precursor, an alternative pathway for NAD biosynthesis [2]. NMRK2 is important for maintaining cardiac function, muscle metabolism, and is also associated with energy metabolism adaptation in certain cancers [1,3,4]. Mouse models have been crucial in studying its functions [1,5].

In Nmrk2 -/- mice, a progressive dilated cardiomyopathy (DCM)-like phenotype was observed with aging, along with eccentric remodeling of the left ventricle, decline in ejection fraction, and reduced myocardial NAD levels at 24 months [1]. Also, old Nmrk2 -/- mice showed an altered response to endurance exercise training, with a maladaptive metabolic response in cardiac and skeletal muscle, though NMRK2 seems dispensable for maintaining global NAD levels in these tissues [5]. In Xp11.2 translocation renal cell carcinoma (tRCC), knockdown of NMRK2 weakened mitochondrial respiration [3].

In summary, Nmrk2 is essential for maintaining cardiac structure and function, and for NAD biosynthetic pathways during aging [1]. In diseases like DCM and Xp11.2 tRCC, Nmrk2 -/- mouse models have revealed its role in cardiac function decline and cancer-related energy metabolism respectively, highlighting its potential as a therapeutic target in these disease areas.