Fam50a, a gene encoding a nuclear protein, is involved in mRNA processing, especially as a component of the spliceosome complex C, and may act as a DNA-binding protein or transcription factor [2,4,5]. It is associated with various biological processes and diseases.

In cancer, integrative pan-cancer analysis shows that Fam50a mRNA level is upregulated in 20 out of 33 types of common cancer tissues. In 8 of these 20 types, upregulation is accompanied by promoter hypomethylation. Elevated expression in 10 types of cancer tissues is linked to poor prognosis. Fam50a knockdown causes DNA damage, induces interferon beta and interleukin-6 expression, and represses cancer cell proliferation, invasion, and migration [1]. In colorectal cancer, knockdown of Fam50a decreases cell proliferation, increases the number of cells in the S phase, and reduces CyclinA2 and CDK2 levels, suggesting its role in regulating tumor progression via the CyclinA2/CDK2 pathway [3]. In hepatocellular carcinoma, it has cancer-promoting effects, can regulate the tumor immune microenvironment, and serves as a diagnostic marker, immunomodulator, and therapeutic target [4]. In Kaposi's sarcoma-associated herpesvirus-induced cellular transformation, FAM50A is crucial, and its knockout inhibits viral-driven proliferation, cellular transformation, and tumorigenesis by altering SHP2 splicing and reducing STAT3 Y705 phosphorylation [5].

For neurodevelopmental disorders, mutations in Fam50a cause Armfield XLID syndrome, a spliceosomopathy. The fam50a knockout zebrafish model exhibits abnormal neurogenesis and craniofacial patterning, with dysregulation of the transcriptome, augmented spliceosome mRNAs, and depletion of neurodevelopment-related transcripts. A unique DNA methylation episignature associated with this disorder has also been detected [2,6].

In summary, Fam50a plays significant roles in cancer development and neurodevelopmental disorders, and gene knockout models, such as in zebrafish for neurodevelopmental studies and in cancer cell lines for cancer-related research, have been instrumental in revealing these functions.