Adnp2, also known as KIAA0863 or ZNF508, is a member of the activity-dependent neuroprotective protein (ADNP) family. It contains a homeobox-profile and is evolutionarily conserved across different phyla [3]. Adnp2 is involved in multiple biological processes, such as regulating retrotransposons, playing a role in neurodevelopment, and influencing cellular viability under oxidative stress [2,3]. Genetic models, like gene-knockout models, are valuable for studying its functions.

In zebrafish, adnp2 mutant models generated using CRISPR/Cas9 showed developmental delays, brain deficits, and core behavioral features of neural developmental disorders (NDDs). RNA-sequencing analysis of their larval brains revealed altered gene expression profiles affecting synaptic transmission, autophagy, apoptosis, microtubule dynamics, hormone signaling, and circadian rhythm regulation [1]. In mammals, genetic ablation of Adnp2 alleviates repression of endogenous retroviruses (ERVs) and long interspersed elements (LINEs), indicating its role in retrotransposon control. When combined with ADNP depletion, the effect is synthetically exacerbated [2]. In P19 embryonic carcinoma cells, RNA silencing of Adnp2 significantly changed the toxicity induced by hydrogen peroxide, similar to what was predicted for Adnp deficiency, suggesting its role in cellular survival pathways [3].

In conclusion, Adnp2 is essential for proper neurodevelopment and retrotransposon control. The study of Adnp2 using gene-knockout models has provided insights into its functions in neural development and has implications for understanding the pathogenesis of NDDs. Additionally, its role in cellular survival pathways under oxidative stress further emphasizes its importance in maintaining cellular homeostasis [1,2,3].