Features include always present findings: Epidermal acanthosis, Acantholysis, Abnormal blistering of the skin, and Scaling skin and others; and common findings: Fragile skin, Angular cheilitis, Cheilitis, and Punctate palmoplantar hyperkeratosis and others. 17 total HPO annotations.

CAST encodes calpastatin (708 aa). Specific inhibition of calpain (calcium-dependent cysteine protease).

Peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome is associated with mutations in the CAST gene on chromosome 5.

The CAST protein participates in Assembly of RNA Polymerase I Holoenzyme (human) and ER-alpha glucosidases bind ER-alpha glucosidase inhibitors pathways.

CAST is classified as a druggable target (Protease Inhibitor category) with score 2.1.

Genetic testing for CAST is available. Testing is considered confirmatory for diagnosis.

Phenotype severity distribution: 7 always present features, 5 common features.

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).

No clinical trials have been registered for peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome.

4 publications have been identified in PubMed for peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome. Research spans Case Report / Case Series (75%) and Review / Meta-Analysis (25%).

Recent Publications

• Alkorashy M (2025). [PMID: 41300744](https://pubmed.ncbi.nlm.nih.gov/41300744/). *Genes*. [Case Report / Case Series]

• Haxho F (2025). [PMID: 40387456](https://pubmed.ncbi.nlm.nih.gov/40387456/). *Pediatric dermatology*. [Review / Meta-Analysis]

• Srinivas SM (2025). [PMID: 39931923](https://pubmed.ncbi.nlm.nih.gov/39931923/). *Pediatric dermatology*. [Case Report / Case Series]

• Nguyen C (2024). [PMID: 38994911](https://pubmed.ncbi.nlm.nih.gov/38994911/). *Pediatric dermatology*. [Case Report / Case Series]