Nptx1, encoding neuronal pentraxin 1, is a secreted protein involved in various cellular and synaptic functions [1]. It has been associated with different biological processes and disease conditions, though the exact associated pathways remain under exploration. Genetic models, such as gene knockout or conditional knockout mouse models, could potentially be valuable for further understanding its functions.

Mutations in Nptx1 have been linked to autosomal dominant cerebellar ataxias. Missense variants in Nptx1, like c.1165G>A (p.G389R) and c.980A>G (p.E327G), have been identified in affected families [1]. These variants can lead to endoplasmic reticulum stress mediated by ATF6, and for one variant, a destabilization of NP1 polymers in a dominant-negative manner, resulting in cerebellar ataxia [1].

In cancer research, Nptx1 seems to have variable roles. In gastric cancer, its high expression is correlated with poor overall survival, and knockdown of Nptx1 attenuates cell migration, invasion, and adhesion abilities, with gene set enrichment analysis showing its positive relation to integrin and focal adhesion [2]. Conversely, in pancreatic and colon cancer, Nptx1 overexpression inhibits cell proliferation, migration, and invasion, and enhances chemotherapy sensitivity [3,6]. In pancreatic cancer, secreted Nptx1 acts on the AMIGO2 receptor to drive metastatic colonization of the liver and is involved in HIF1α nuclear retention [4]. In thymoma, Nptx1 is highly expressed and has diagnostic value [5].

In conclusion, Nptx1 is a multifaceted gene involved in both neurological and cancer-related processes. Its role in autosomal dominant cerebellar ataxias, as revealed through the identification of causative mutations, provides insights into the disease mechanism. In cancer, its context-dependent functions in different cancer types highlight its potential as a prognostic indicator and a therapeutic target. The study of Nptx1 using gene knockout or conditional knockout mouse models could further elucidate its underlying molecular mechanisms in these disease areas.