Microtubule affinity-regulating kinase 4 (MARK4)

Microtubule affinity-regulating kinase 4 (MARK4) is a serine/threonine protein kinase that regulates the stability and organization of microtubules by phosphorylating microtubule-associated proteins such as tau, MAP2, and MAP4[2][8]. MARK4 is structurally related to the AMPK/Snf1 kinase family and is expressed predominantly in the brain, where it localizes to microtubules and the centrosome[2][8]. It plays a critical role in microtubule bundle formation, cell polarity, and neuronal process outgrowth. Dysfunction or abnormal overactivity of MARK4 is implicated in neurodegenerative diseases such as Alzheimer’s disease through tau hyperphosphorylation, and it may also contribute to cancer pathophysiology by altering microtubule dynamics and cell cycle progression[1][2]. The protein structure contains a catalytic (kinase) domain, a UBA (ubiquitin-associated) domain, and other regulatory elements[1][3]. Several small molecule inhibitors targeting MARK4's kinase activity have been structurally characterized, but no clinical drugs are currently approved against this target[3].

Other names

MAP/microtubule affinity-regulating kinase 4MARK4PAR-1DKIAA1860FLJ90097MARKL1Nbla00650

Inhibition of kinase activity (ATP-competitive inhibition); Prevention of tau phosphorylation (for relevant inhibitors)