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The study investigates NF-κB signalling in CYLD cutaneous syndrome (CCS) tumours to identify potential drug targets. Researchers used transcriptomics, proteomics, and single-cell RNA sequencing on patient-derived CCS tumour cells, revealing evidence of non-canonical NF-κB signalling with increased p100 to p52 processing and RelB protein expression. IκB kinase alpha (IKKα) was identified as a candidate target, and a novel IKKα inhibitor (SU1644) was tested on CCS tumour spheroid cultures, showing reduced tumour viability. The findings support the potential use of topical IKKα inhibitors as a preventive treatment for CCS.