The COP9 signalosome (CSN) is a protein complex consisting of 9 subunits, with CSN5 serving as the catalytic subunit. CSN influences protein degradation by removing the ubiquitin-like modifier Nedd8 from cullin-based E3 ubiquitin ligases, thereby inactivating them. Although the ubiquitin-proteasome system plays a crucial role in numerous neuronal processes, the specific role of CSN in brain development remains unclear. In this study, we aimed to elucidate the impact of CSN loss-of-function at various stages of neuronal development in mice. We utilized the Cre-loxP system to knock out (KO) the CSN5 subunit. The knockout of CSN5 in proliferating neuroblasts using the Nestin-Cre line resulted in embryonic lethality, likely due to disrupted cell division. When combining the CSN5 line with the Nex-Cre recombinase, we found that conditional KO of CSN5 in early postmitotic excitatory neurons was lethal at postnatal day (PD) 1. In contrast, CSN5 deletion in inhibitory neurons using the Dlx-Cre recombinase results in lethality between PD 17 and 21. Furthermore, CSN5 deletion in mature excitatory forebrain neurons did not affect lifespan or gross brain morphology. Our findings suggest that CSN plays developmental stage-dependent roles in the brain. These roles may vary depending on the type of neuron, underscoring the complexity of CSN functions in neurodevelopment.