FOCAD, also known as KIAA1797, encodes a novel focal adhesion protein with tumour suppressor function in gliomas [4]. It is involved in multiple biological processes. FOCAD is part of the SKI messenger RNA surveillance pathway, playing a role in maintaining liver homeostasis [1]. It also affects microtubule assembly, G2/M progression in astrocytic gliomas, and is associated with the prognosis of patients with IDH-mutant astrocytic gliomas [3]. Additionally, FOCAD is negatively regulated by EGR1 in gastric cancer, acting as a tumour suppressor by inhibiting cell proliferation and migration [2].

In zebrafish lacking focad, it phenocopied the human pediatric liver cirrhosis disease, revealing altered mRNA degradation processes in the liver [1]. In human hepatic cell lines with CRISPR-Cas9-mediated FOCAD inactivation, the SKI mRNA surveillance pathway was compromised due to reduced levels of the RNA helicase SKIC2 and its cofactor SKIC3. FOCAD knockout hepatocytes showed lowered albumin expression, signs of persistent injury, and CCL2 overproduction [1]. In astrocytic gliomas, FOCAD loss was associated with inferior patient outcome. It interacted with tubulin beta-6 and other tubulin family members, influencing microtubule assembly and G2/M progression [3].

In conclusion, FOCAD is crucial for maintaining normal biological functions in the liver and in gliomas. Gene-knockout models, such as zebrafish lacking focad and FOCAD-inactivated human hepatic cell lines, have been instrumental in revealing its role in liver-related diseases and glioma development. These findings provide potential therapeutic targets, like the CCL2/CCR2 signaling axis in liver cirrhosis and understanding the implications of FOCAD loss in gliomas [1,3].