NSMF (NMDA receptor synaptonuclear signaling and neuronal migration factor) is a multifunctional protein with primary roles in neuronal development and genome maintenance. Mechanistically, NSMF mediates synaptic-to-nuclear signaling downstream of NMDA receptor activation, transporting from synapses to the nucleus to regulate activity-dependent gene expression 1. The protein couples glutamate receptor signaling to transcriptional changes affecting dendritic morphogenesis and spine plasticity. During early postnatal development, NSMF facilitates BDNF-induced nuclear import critical for hippocampal development 1. Additionally, NSMF functions as a replication stress response factor that localizes to stalled replication forks and scaffolds the RPA-CDC5L-ATR complex to activate ATR signaling for DNA damage response 2. NSMF also modulates replication fork progression under stress, balancing genomic instability in cancer cells 3. Disease relevance includes hypogonadotropic hypogonadism 9, where NSMF mutations impair hypothalamic and ovarian gene expression affecting fertility 4. In colorectal cancer, elevated NSMF expression enables cancer cell survival under replication stress, making it a potential therapeutic target 3. Thus, NSMF integrates neuronal signaling and genome maintenance functions essential for both neurodevelopment and cancer progression.