KLK3 and pachyonychia congenita: Castrate-resistant prostate cancer (CRPC) is progressive prostate cancer (PC) metastases in men.[1–5] It is characterized by a continuous rise in serum prostate-specific antigen levels.[6–10] It has been estimated that about 165,000 new PC cases, and 30,000 patients will die from PC.[11,12] Despite most patients with PC are cured, 20% of them may experience recurrence of this disease.[13] Although androgen deprivation therapy is utilized for the treatment of patients with recurrent, progressive, or metastatic PC, most of them will eventually develop CRPC.[14,15]