Aplp2, also known as amyloid precursor-like protein 2, is a member of the APP family. It has diverse functions and is involved in multiple biological processes. Aplp2 shares a similar structural organization with APP and APLP1, and they have partially overlapping functions. APP family proteins are essential for survival as shown by knockout mouse cross-breeding analysis [1]. Aplp2 has been implicated in pathways such as TGF-β signaling, NF-κB signaling, and JNK-mediated cell migration [2,3,4].

In gene knockout models, Aplp2 mutant mice show heightened susceptibility to mycobacterial infection with decreased inducible nitric oxide synthase (iNOS) expression and cytokine production, indicating its role in safeguarding against mycobacterial infections [3]. Aplp2 knockout mice also develop high degrees of hyperopia and exhibit a dose-dependent reduction in susceptibility to environmentally induced myopia, suggesting its importance in refractive development [6]. In addition, in spinal GABAergic inhibitory neurons, targeted knockdown of Aplp2 in GAD2-Cre mice evokes pain hypersensitivity by means of microglia activation [5].

In conclusion, Aplp2 plays crucial roles in multiple biological processes including immune defense against mycobacterial infections, refractive development, and pain sensitivity regulation. Gene knockout mouse models have been instrumental in revealing these functions, contributing to our understanding of diseases related to these processes such as tuberculosis, myopia, and neuropathic pain.