Hpcal1-KO Mouse

Hpcal1, also known as hippocalcin like 1, serves as a calcium ion (Ca2+) sensor and is involved in multiple biological processes. It participates in selective autophagy, specifically acting as an autophagy receptor in ferroptosis, and is associated with pathways like Wnt/β-catenin signaling. It also has significance in cancer development, lipid metabolism, and may be a biomarker for certain diseases [1,2,3,4,5].

In a study using Hpcal1 null mice, Hpcal1 was identified as a negative regulator of de novo lipid biosynthesis and mTOR signaling activation, limiting liver tumorigenesis [4]. Genetic loss of Hpcal1 made hepatocellular carcinoma (HCC) mTORC1-addicted and sensitive to mTOR inhibitor AZD-8055 in vitro and in vivo. Additionally, the genetic or pharmacological inhibition of Hpcal1 prevented ferroptosis-induced tumor suppression and pancreatitis in mouse models [1].

In conclusion, Hpcal1 plays essential roles in processes such as autophagy-dependent ferroptosis, lipid metabolism, and cancer-related signaling pathways. Mouse models with Hpcal1 knockout or knockdown have revealed its significance in liver tumorigenesis and ferroptosis-related diseases, providing insights into potential therapeutic strategies for these conditions.