Nosip, short for nitric oxide synthase-interacting protein, is a significant protein that interacts with nitric oxide synthase (NOS) and modulates NO synthesis and release, thereby participating in multiple physiological and pathological processes [1,3,4,5]. It is involved in pathways related to cell proliferation, apoptosis, and migration, and is crucial for normal development, especially of the neural and craniofacial systems [2,6,7]. Genetic models like mouse and Xenopus have been valuable in studying Nosip's functions.

In mouse models, Nosip knockout leads to craniofacial defects, holoprosencephaly, and reduced brain size with impaired neural stem cell/progenitor self-renewal and neurogenesis [6,7]. In Xenopus, Nosip knockdown results in microcephaly, defects in eye formation, and disrupted cranial cartilage structures [2]. In hepatocellular carcinoma (HCC) cells, Nosip acts as an oncogene; its knockdown inhibits cell proliferation, motility, and promotes apoptosis, while overexpression has the opposite effects [1]. In the context of Hirschsprung's disease, NOSIP expression is increased in the colon, potentially contributing to enterocolitis by inhibiting local NO production [8].

In summary, Nosip is essential for normal development, including neural and craniofacial development. Its dysregulation is associated with various diseases such as HCC and Hirschsprung's disease. The use of gene knockout models in mouse and Xenopus has been instrumental in uncovering Nosip's functions and its implications in disease, providing insights into potential therapeutic targets for related disorders.