RESEARCH SUMMARY The proposal will study the unusual phenotype of a 69-year-old woman who displays exceptionally accelerated skin wound healing with minimal scarring. Genome sequencing revealed that her phenotype is caused by an ~8 kb deletion downstream of the fatty acid aldehyde hydrolase (FAAH) gene that results in the loss of a long noncoding RNA (lncRNA) gene named FAAH OUT. The goal of this proposal is to understand how the FAAH OUT deletion results in accelerated wound healing. In the United States, the annual medical burden of chronic wounds exceeds $25 billion and continues to rise with the aging population. There is a critical need to improve understanding of the biological processes underlying skin wound healing and to innovate new therapies. In the first aim, we will study normal and wounded skin tissue from the study subject using spatial transcriptomics, in situ hybridization, and xenograft skin repair models to understand how the FAAH OUT locus regulates wound healing. In the second aim, we will elucidate the FAAH OUT genetic interactome to gain insight to its molecular mechanisms. By studying a rare genetic allele of an individual with markedly enhanced wound healing, this proposal aims to generate novel insight to the role of lncRNAs in wound repair and discover new human-validated targets to treat cutaneous wounds.