Aplp2, also known as amyloid precursor-like protein 2, belongs to the APP family. It shares a similar structural organization with APP and APLP1, and has partially overlapping functions. APP family proteins are essential for survival. Aplp2 is involved in multiple biological processes and signaling pathways. For instance, it may play a role in TGF-β signaling [1], JNK-dependent cell migration [2], and is also associated with nociceptive information processing [3], mycobacterial infection defense [4], neuronal stem cell differentiation [5], refractive error and myopia development [6], and is related to the prognosis and clinicopathology of renal cell carcinoma [7], as well as lipid levels in the Chinese population in Xinjiang [8], and the regulation of MHC class I molecules on irradiated Ewing's sarcoma cells [9].

In mouse models, Aplp2 knockout mice develop high degrees of hyperopia and show a dose-dependent reduction in susceptibility to environmentally induced myopia, suggesting its important role in refractive development [6]. In addition, targeted knockdown of Aplp2 in GABAergic interneurons of GAD2-Cre mice evokes pain hypersensitivity by means of microglia activation, revealing its role in pain sensitivity regulation [3]. Mice with Aplp2 mutation or knockdown exhibit diminished macrophage-mediated killing of Mycobacterium tuberculosis, accompanied by decreased inducible nitric oxide synthase (iNOS) expression and reduced cytokine production, indicating its role in mycobacterial infection defense [4].

In conclusion, Aplp2 is crucial for multiple biological functions including cell migration, pain sensitivity, mycobacterial infection defense, and refractive development. The use of gene knockout or knockdown mouse models has significantly contributed to understanding its role in these biological processes and related disease conditions such as myopia, neuropathic pain, and tuberculosis.