Development of the brain and central nervous system is a complex process involving localized gene expression and regulated cell death and proliferation. Here, we describe a gene involved in neuronal survival, the zebrafish ortholog of the human lzic gene. Zebrafish lzic is expressed ubiquitously during early development and later becomes enriched in the developing brain. Using antisense morpholino oligonucleotides, we demonstrate that zebrafish lzic is required zygotically for the survival of distinct neuronal populations. LZIC is closely related to ICAT, a physiological inhibitor of the Wnt pathway that interacts physically and functionally with beta-catenin to prevent the transcription of Wnt target genes. LZIC's ICAT-homologous region is highly similar to ICAT with particular conservation of residues that are used by ICAT for beta-catenin-binding. Surprisingly, despite this high similarity, LZIC does not interact with beta-catenin in vitro or in vivo. Our results reveal that LZIC, a protein conserved in vertebrates, is required for neuronal survival in zebrafish.