PIANP is a primarily neuronally localised protein which binds to the N-terminal domain of GABA-B receptors as well as the inhibitory immunoglobuline-like type 2 receptor PILRa [1]. In humans, a homozygous loss-of-function mutation of PIANP is associated with features of intellectual disability and global development delay whilst PIANP knockout mice display autism spectrum disorder (ASD)-like behaviour as well as heightened anxiety [2]. As we previously reported, PIANP knockout mice present with a different composition of telencephalic cell layers and increased neuronal apoptosis [2, 3]. Here, we analysed male homozygous knockout mice (PIANPcre) and compared them to both mutant mice floxed at the PIANP locus (PIANPflp) and wildtype C57Bl6/N mice. We observed changes of gross cerebellar morphology, as well as quantitative alterations of adult hippocampal neurogenesis in knockout mice. Interestingly enough, these alterations affect both proliferative as well as apoptotic processes. Furthermore, PIANP knockouts showed altered cerebellar histoarchitecture compared to wildtype mice, which seems to be influenced by both structural and cellular alterations. Taken together, these results unveil additional factors which seem to be involved in the observed ASD-like phenotype of PIANP knockout mice. Further research is necessary to map the precise influences of these individual changes and their interplay in effecting the above-mentioned behaviour observed in both humans and mice.Bibliography:1. Kogure A, et al. Biochem Biophys Res Commun. 2011;405:428–433.2. Winkler M et al. Mol Psychiatry. 2020;25:2979–2993.3. Winkler M et al. Mol Psychiatry. 2020;25:2645–2645.