Trichohyalin (TCHH) is a structural protein responsible for the proper cylindrical fiber topology of the hair shaft. TCHH binds other TCHH and keratin-intermediate filaments creating the proper cross-links and cylindrical shape of the hair shaft. PADI3 and TGM3 are two enzymes responsible for post-translational modification of TCHH important for cross-linking of TCHH within the hair. In Uncombable Hair Syndrome mutations in TCHH, PADI3, or TGM3 result in improper cross-linking and the resulting irregular shape of the hair shaft.The particular defect in TCHH as a structural component of hair may be a defect of deimination. Deimination converts the amino acid arginine to the amino acid citrulline. This conversion is done by calcium-dependent enzymes known as peptidylarginine deiminases (PADs). PADI3 is a member of this enzyme class. One study reported PAD involvement in skin and skin-related diseases, particularly at the hair follicle. Alterations to PAD activity resulted in the development of Uncombable Hair Syndrome. Another study examined the transglutaminase (TG) family of enzymes and their involvement in UHS. This family of enzymes includes TGM3, which is expressed in epidermal cells. Mutations in TGM3 may therefore reduce or alter the intermolecular cross-linking important for hair shaft formation, leading to Uncombable Hair Syndrome.Another molecular mechanism of UHS was proposed by Ralph Trueb in 2003. He suggested that premature keratinization of the inner hair root forms a rigid sheath that alters the shape of a hair strand as it grows out of the root.
This is in part due to the large variety of organisms living in the urinary tract. Ureaplasma urealyticum and Mycoplasma genitalium are some of the culprits. NGU is also associated with reactive arthritis, in which the triad of arthritis, conjunctivitis, and urethritis is seen. Bacterial
The most common bacterial cause of NGU is Chlamydia trachomatis, but it can also be caused by Ureaplasma urealyticum, Haemophilus vaginalis, Mycoplasma genitalium, Mycoplasma hominis, Neisseria meningitidis, Gardnerella vaginalis, Acinetobacter lwoffii, Acinetobacter calcoaceticus,  and E.coli. Viral
Herpes simplex virus, Adenovirus,
Cytomegalovirus

Fungi
Candida Albicans

Parasitic
Parasitic causes include Trichomonas vaginalis (rare). Noninfectious
Urethritis can be caused by mechanical injury (from a urinary catheter or a cystoscope), or by an irritating chemical (antiseptics or some spermicides). Diagnosis
It has been easy to test for the presence of gonorrhea by viewing a Gram stain of the urethral discharge under a microscope: The causative organism is distinctive in appearance; however, this works only with men because other non-pathogenic gram-negative microbes are present as normal flora of the vagina in women. Thus, one of the major causes of urethritis can be identified (in men) by a simple common test, and the distinction between gonococcal and non-gonococcal urethritis arose for this reason. Non-gonococcal urethritis (NGU) is diagnosed if a person with urethritis has no signs of gonorrhea bacteria on laboratory tests. The most frequent cause of NGU (23%-55% of cases) is C. trachomatis.