Cacybp, also known as Calcyclin-Binding Protein and Siah-1 Interacting Protein (CacyBP/SIP), is a small modular protein involved in a wide range of cellular processes [1,4]. It binds to several target proteins like S100 family members, components of the ubiquitin ligase complex, and cytoskeletal proteins. CacyBP is implicated in protein de-phosphorylation, ubiquitination, cytoskeletal dynamics, regulation of gene expression, cell proliferation, differentiation, and tumorigenesis [1]. It is expressed in different mammalian tissues, with high levels in tumor cells and neurons [1]. Genetic models can be valuable in further exploring its functions.

Knockdown of CacyBP inhibits the proliferation, migration, and tumorigenicity of prostate cancer cells, and this effect is alleviated by adding a p53 inhibitor, suggesting its role in prostate cancer progression via p53 [2]. In bladder cancer, downregulation of CacyBP by CRISPR/dCas9-KRAB inhibits cell proliferation and migration and promotes apoptosis, indicating it as an important oncogene in bladder cancer [5]. Blockage of CacyBP in hepatocellular carcinoma diminishes the infiltration of tumor-associated macrophages and improves the efficacy of anti-PD-1 therapy [3]. In lung adenocarcinoma, CacyBP promotes tumorigenesis by regulating the tumour suppressor OTUD5 [6]. In p53 mutant glioma cells, CacyBP/SIP reduces p53 stability by enhancing Mdm2 activity [7].

In conclusion, CacyBP is a multi-functional protein involved in various cellular processes and plays a significant role in multiple cancers including prostate, bladder, hepatocellular, lung adenocarcinoma, and glioma. Loss-of-function experiments, such as knockdowns and downregulations, have revealed its oncogenic potential in these cancer types, providing potential therapeutic targets. [2,3,5,6,7]