TRRAP, short for transformation/transcription domain-associated protein, is a key adaptor protein and a component of histone acetyltransferase (HAT) complexes. Structurally, it belongs to the phosphoinositide 3-kinase-related kinases (PIKK) family but is a pseudokinase. It functions in gene transcription regulation by acting as a scaffold for multiple transcription factors and HAT complexes, being involved in processes like cell cycle progression, stemness maintenance, and neural homeostasis [1].

In zebrafish, trrap gene-knockout led to smaller eyes, heads, reduced ventral pharyngeal arch size, and impaired tooth mineralization, with changes in dlx3 and dlx2b expression, suggesting its role in craniofacial development [3]. In mouse models, Trrap deletion in Purkinje neurons caused neurodegeneration in old mice, and TRRAP was found to be required for SP1-mediated regulation of microtubule dynamics [4]. In colon cancer cells, TRRAP knockdown decreased the expression of a cancer stem cell marker and spheroid-forming ability, and enhanced the expression of a tumor suppressor gene, indicating its role in tumorigenicity [2].

In conclusion, TRRAP is essential for gene transcription regulation through its role in HAT complex assembly and interaction with transcription factors. Model-based research, especially gene-knockout models in zebrafish and mice, has revealed its importance in craniofacial development, neurodegeneration prevention, and tumorigenesis, providing insights into related disease mechanisms.