Fam163a, also called neuroblastoma-derived secretory protein (NDSP) or C1ORF76, was newly found on chromosome 1q25.2. It has been implicated in multiple biological processes. In the ERK signaling pathway, it acts as a positive regulator, interacting with 14-3-3β to promote cell proliferation in squamous cell lung carcinoma [1]. It may also be part of the mitochondrial proteome, playing a role in the regulation of food intake, AgRP neuron activity, and mitochondrial function in the hypothalamus [2]. Additionally, it is associated with ocular axial length and refractive error in Chinese populations, suggesting a role in myopia-related processes [3,4].

In a mouse model, knockdown of Fam163a in the arcuate nucleus of the hypothalamus increased short-term cumulative food intake, increased Pomc mRNA expression, reduced leptin levels, and decreased the firing frequency of AgRP neurons. It also differentially regulated the expression of genes related to mitochondrial biogenesis, mitophagy, fusion, and oxidative stress [2]. In squamous cell lung carcinoma, overexpression of Fam163a increased ERK and p90RSK phosphorylation, promoted cyclin D1 expression, and enhanced cell proliferation, which could be reversed by U0126 [1].

In conclusion, Fam163a plays essential roles in cell proliferation, metabolism-related neuronal regulation, and potentially in myopia-related processes. The knockdown studies in mouse models have provided insights into its role in hypothalamic-regulated metabolism, while in vitro and in vivo studies in lung carcinoma have illuminated its function in promoting cancer cell proliferation. These findings contribute to understanding the underlying mechanisms of related diseases and may offer potential therapeutic targets.