Myotubularin-related protein 5 (MTMR5) (MTMR5)

Myotubularin-related protein 5 (MTMR5), also known as Set binding factor 1 (SBF1), is a member of the myotubularin family of phosphoinositide phosphatases that acts as a catalytically inactive pseudophosphatase [1]. It functions primarily as a regulatory binding partner for MTMR2, significantly increasing MTMR2's enzymatic activity against phosphatidylinositol 3-phosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) [2]. This interaction is essential for maintaining proper membrane trafficking and myelin sheath integrity in the peripheral nervous system [3]. Mutations in the MTMR5/SBF1 gene are a known cause of Charcot-Marie-Tooth disease type 4B3 (CMT4B3), a recessive demyelinating neuropathy characterized by myelin outfoldings [4]. Additionally, MTMR5 is critical for spermatogenesis, and its deficiency is associated with azoospermia and male infertility [5]. While no small molecule drugs currently target MTMR5, its mRNA and gene are focal points for developing genetic therapies, including antisense oligonucleotides (ASOs) and viral-mediated gene replacement, to restore the functional MTMR2-MTMR5 complex in affected tissues [6]. Citations: [1] UniProt Consortium (O95248); [2] Berger et al. (2003) Human Molecular Genetics; [3] Firestein et al. (2002) Journal of Biological Chemistry; [4] Nakhro et al. (2013) Neurology; [5] Ge et al. (2014) Development; [6] Bolino et al. (2016) Expert Opinion on Orphan Drugs.

Other names

Set binding factor 1SBF1DENND7AMTMR5 mRNA

Modulation of MTMR2 phosphatase activity or restoration of SBF1/MTMR5 function through gene therapy or RNA-based therapeutics.