LAUSR

Activity-dependent neuroprotective protein (ADNP) was discovered by the Gozes laboratory (Bassan et al. 1999; Gozes et al. 1999). Initial studies suggested that this protein is secreted from glial cells in the presence of vasoactive intestinal peptide (VIP), to further mediate VIP’s neuroprotective activity (Bassan et al. 1999; Furman et al. 2004). The human ADNP (hADNP) gene structure (~ 40 kb) includes five exons and four introns with alternative splicing of an untranslated second exon (chromosome 20q12-13.2, a region associated with aggressive tumor growth) (Zamostiano et al. 2001; Gozes et al. 2015b). With its key regulatory functions, ADNP controls the expression of more than 400 genes during embryonic development (Mandel et al. 2007) and of thousands of hippocampal genes postnatally, impacting pathways associated with ion channelssynaptic transmission in a sexand age-dependent manner (Amram et al. 2016). Thus, ADNP is essential for brain formation with complete knockout resulting in neural tube closure defects and embryonic death in the mouse (Pinhasov et al. 2003) and with haploinsufficiency (heterozygosity) resulting in cognitive deficits (Vulih-Shultzman et al. 2007) as well as developmental delays and motor and vocalization impediments (Hacohen-Kleiman et al. 2018). In humans, an ADNP gene deletion was first implicated in delayed cognitive development in a case study in 2007 (Borozdin et al. 2007). Later, a syndrome with multiple body organ involvements and neurodevelopmental delay named