Furthermore, several different pathogenic mechanisms have been identified: (1) intra-mitochondrial localization of mutant SOD1 has been correlated with mitochondrial dysfunction; (2) levels of ATP/oxygen consumption/respiratory chain enzymes are decreased in Mn cell lines expressing mutant human SOD1; (3) expression of CB-D28K and parvalbumin is significantly decreased in Mn lost in the early stages of ALS [145] whereas calreticulin is downregulated in neuronal models of ALS. The gene discussed is CALR; the disease is amyotrophic lateral sclerosis.