Smtnl2, also known as smoothelin-like 2, is a member of the smooth-muscle-related Smoothelin protein family. It binds to actin filaments and is involved in epithelial morphogenesis. It may also be related to muscle-specific functions as its expression is high in skeletal muscle. It has been associated with pathways like glucose metabolism in Sertoli cells and actin cortex regulation in epithelial cells [2,3,4].

In Smtnl2-deficient Sertoli cells, there is a defective ability to engulf apoptotic germ cells despite normal phagosome maturation, indicating its role in the engulfment process through regulating the function of ARP3. Also, depletion of Smtnl2 in Sertoli cells leads to a shift in glucose metabolism restricting lactate production, activating downstream AMPK and AKT signaling. In vivo RNAi-mediated silencing of Smtnl2 in testis disrupts cytoskeleton architecture and blood-testis barrier integrity, causing germ cell detachment [1]. In epithelial cells, Smtnl2 deficiency leads to membrane herniations in the apical domain, suggesting its role in stabilizing the apical actin cortex by inhibiting coronin-1B [3].

In conclusion, Smtnl2 is crucial for Sertoli cell function in supporting spermatogenesis, as well as for epithelial morphogenesis by regulating actin dynamics. The use of gene-knockdown models, such as RNAi in vivo and gene-deficient cell models, has been instrumental in revealing its functions in these biological processes. These findings contribute to understanding related diseases such as spermatogenesis-related disorders and epithelial-related pathologies [1,3].