PGBD1 is a mammal-specific domesticated transposase derived from piggyBac DNA transposons that has lost transposition activity but retained DNA-binding capability 1. Although the gene body retains much of the original transposon sequence and has captured SCAN and KRAB domains, PGBD1 no longer recognizes piggyBac inverted repeats 1. Genome-scale analysis reveals enriched binding sites in and around genes involved in neuronal development, with associations to both histone activating and repressing marks 1. PGBD1 specifically binds the promoter and gene body of NEAT1, a long noncoding RNA encoding the core structural component of neuronal paraspeckles 1. PGBD1 depletion in neuronal progenitor cells increases NEAT1 expression and paraspeckle formation, impairing cellular differentiation 1. This suggests PGBD1 evolved core regulatory functions maintaining neural progenitor cell identity. Regarding disease relevance, PGBD1 has been implicated in schizophrenia susceptibility through genome-wide association studies, with polymorphisms at chromosome 6-p22.1 showing significant association in multiple populations 23. Additionally, PGBD1 variants show suggestive association with age-at-onset in late-onset Alzheimer's disease 4. The gene represents a rare example of evolutionary acquisition of novel function coupled with emergence of a mammal-specific cellular structure.