Causes
HPS can be caused by mutations in several genes: HPS1, HPS3, HPS4, HPS5, HPS6 and HPS7.HPS type 2, which includes immunodeficiency in its phenotype, is caused by mutation in the AP3B1 gene.HPS type 7 may result from a mutation in the gene coding for dysbindin protein.Hermansky–Pudlak syndrome is thought to be inherited as an autosomal recessive genetic trait. The defective gene, called HSP, responsible for this disorder is located on the long arm of chromosome 10 (10q2). Some research suggests that an abnormality of lysosomal function may be responsible for the development of the disease. HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1 and  Biogenesis of Lysosome-related Organelles Complex (BLOC1, BLOC1S2 and BLOC3) are associated with Hermansky–Pudlak syndrome.In autosomal recessive disorders, the condition does not appear unless a person inherits two copies of the defective gene responsible for the disorder, one copy coming from each parent. If an individual receives one normal gene and one gene for the disorder, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.
Cause
While the exact cause is unknown, the genetic predisposition to GPS involves the human leukocyte antigen (HLA) system, specifically HLA-DR15. In addition to genetic susceptibility, an initial environmental insult to the pulmonary vasculature is needed to allow the anti-glomerular basement membrane (anti-GBM) antibodies to reach the alveolar capillaries. Examples of such an insult include: exposure to organic solvents (e.g. chloroform) or hydrocarbons, exposure to tobacco smoke, infection (such as influenza A), cocaine inhalation, metal dust inhalation, bacteremia, sepsis, high-oxygen environments, and antilymphocyte therapies (especially with monoclonal antibodies). Exposure to dry cleaning chemicals and Paraquat brand weed killer have also been implicated as potential insults. In GPS, anti-GBM antibodies are produced and circulated throughout the bloodstream, damaging the membranes lining the lungs and kidneys as well as targeting their capillaries. Pathophysiology
GPS is caused by abnormal plasma cell production of anti-GBM antibodies. The major target of these abnormal antibodies is the non-collagen domain of the alpha-3 chain of type 4 collagen, which is mostly found in the basal membranes of glomerular and alveolar capillaries, explaining the obscurely specific symptoms of this condition. This preferred targeting of these alpha-3 collagen chains specifically in the basal membranes of glomerular and alveolar capillaries can be explained by the higher accessible exposure of epitopes, a larger expansion of the alpha-3 collagen units, and because these alpha-3 collagen chains structurally provide higher accessibility for the targeting antibodies. These antibodies bind their reactive epitopes to the basement membranes and activate the complement cascade, leading to the death of tagged cells.