Approximately 9% of human proteins still lack a defined function. In a study led by Agnieszka Tudek, Tomecki, Drabko and colleagues provide the first biochemical characterization of the human TTC33 protein and identify a trimeric TTC33–WDR61–PHF5A complex that serves as a hub for interactions with SF3B proteins involved in RNA splicing, PP2A-B55α phosphatase, CCDC97 and DNA repair enzyme UNG1/2. Loss of TTC33 network components leads to genomic instability and delayed cell proliferation, revealing a previously uncharacterized role of TTC33 in maintaining cellular homeostasis. Their work has been published in Nature Communications.