Uaca, also known as Uveal autoantigen with coiled-coil domains and ankyrin repeats (Nucling), is involved in multiple biological functions. It is a key regulator of tumor suppressor Par-4, and is associated with basolateral exosome release in polarized epithelial cells through interaction with Rab39 [1,2]. Uaca has been implicated in exosome-related pathways and may play a role in cellular communication. It also seems to be relevant in processes related to cell proliferation, invasion, and senescence.

Knockdown of Uaca in hepatocellular carcinoma (HCC) cells suppressed their proliferative and invasive ability and promoted senescence [3]. In breast cancer, the Uaca locus was associated with overall survival in patients taking Par-4 dependent chemotherapies, and higher Uaca gene expression was linked to worse overall survival [1]. In urothelial cancer, autoantibodies against Uaca were associated with resistance to immune checkpoint inhibitor (ICI) therapy [4].

In conclusion, Uaca has diverse functions in different biological processes and disease conditions. Studies, especially those using knockdown techniques similar to gene-knockout in concept, have revealed its role in cancer-related processes such as chemoresistance in breast cancer, and in the regulation of malignant behaviors in HCC. These findings contribute to our understanding of the molecular mechanisms underlying these diseases and may have implications for developing new treatment strategies.