The MTM (myotubularin)/MTMR (myotubularin-related) protein family is comprised 
of 15 lipid phosphatases, of which nine members are catalytically active. MTMs 
are known to play a fundamental role in human physiology as gene mutations can 
give rise to X-linked myotubular myopathy or Charcot-Marie-Tooth disease, which 
manifest in skeletal muscle or in peripheral neurons respectively. 
Interestingly, studies have shown MTMR2 and MTMR5, two MTM family members, to be 
highly expressed in the testis, particularly in Sertoli and germ cells, and 
knockout of either gene resulted in spermatogenic defects. Other studies have 
shown that MTMR2 functions in endocytosis and membrane trafficking. In the 
testis, MTMR2 interacts and co-localizes with c-Src/phospho-Src-(Tyr⁴¹⁶), a 
non-receptor protein tyrosine kinase that regulates the phosphorylation state of 
proteins at the apical ES (ectoplasmic specialization), a unique type of cell 
junction found between Sertoli cells and elongating/elongated spermatids. In the 
present review, we highlight recent findings that have made a significant impact 
on our understanding of this protein family in normal cell function and in 
disease, with the emphasis on the role of MTMs and MTMRs in spermatogenesis. We 
also describe a working model to explain how MTMR2 interacts with other proteins 
such as c-Src, dynamin 2, EPS8 (growth factor receptor pathway substrate 8) and 
ARP2/3 (actin-related protein 2/3) at the apical ES and the apical TBC 
(tubulobulbar complex; tubular-like invaginations that function in the 
disassembly of the apical ES and in the recycling of its components) to regulate 
spermiation at late stage VIII of the seminiferous epithelial cycle.