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 multiple biological processes. It has been associated with epithelial morphogenesis, and may also play a role in muscle-related functions considering its high expression in skeletal muscle. It is also potentially involved in pathways related to cell metabolism and cytoskeleton regulation [2,3,4].

In Sertoli cells, Smtnl2-deficient cells show defective ability to engulf apoptotic germ cells, despite normal phagosome maturation. This indicates its role in the efferocytosis process, possibly through regulating the function of the branched actin nucleation protein ARP3. Depletion of Smtnl2 in Sertoli cells also leads to a shift in glucose metabolism, restricting lactate production and 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 conclusion, Smtnl2 is crucial for Sertoli cell function in supporting spermatogenesis, as demonstrated by studies using loss-of-function models. These models have provided insights into its role in processes such as apoptotic germ cell clearance and metabolism regulation, which may have implications for understanding male reproductive disorders [1].