HIVEP3, also known as Schnurri-3 (SHN3), is a gene encoding a zinc finger protein that contains zinc finger and acid-rich (ZAS) domains. It is involved in multiple vital biological processes. HIVEP3 has been associated with pathways like TNF signaling, and it may regulate transcription via the kappaB enhancer motif [6]. It plays a role in cell survival, tumor formation, and is important in the development and function of certain immune cells and in bone-related processes [1,2,4,5]. Genetic models, such as gene-knockout (KO) mouse models, can be valuable for studying its functions.

In acute myeloid leukemia (AML), high HIVEP3 expression is associated with adverse prognosis, and it is related to AML subtypes, age, cytogenetic risk, etc. Knockdown of HIVEP3 in AML cells represses cell proliferation, invasion, and enhances apoptosis, and it inhibits the TGF-β/Smad signaling pathway [1,3]. In CD8+ invariant NKT cells, low HIVEP3 expression in stage 0 cells favors their development and T helper 1-biased cytokine responses [2]. In bone-related studies, mice lacking SHN3 (HIVEP3) show increased bone formation due to de-repression of ERK pathway signaling in osteoblasts, and depletion of Shn3 in Adipoq-lineage progenitors in mice leads to increased trabecular bone mass and enhanced fracture healing [4,5].

In conclusion, HIVEP3 is crucial in multiple biological processes. Its role in AML shows its potential as a prognostic factor and a target for treatment. In the immune system, it influences the development and function of CD8+ invariant NKT cells. In bone, HIVEP3-related KO mouse models have provided insights into bone formation and fracture healing, suggesting potential therapeutic strategies for bone-loss-related disorders.