ACHE (acetylcholinesterase) is a primary cholinesterase that functions to terminate synaptic signal transmission by hydrolyzing acetylcholine at neuromuscular junctions and brain cholinergic synapses. It also constitutes the Yt blood group antigen on red blood cell membranes. Multiple alternatively spliced forms of ACHE are expressed separately in the brain, muscle and erythroid tissues. Dysregulation of ACHE can result in impaired neurotransmission when levels of ACHE are too high, while inhibition of ACHE can lead to muscular paralysis, bronchial constriction and asphyxiation. Direct inhibitors of ACHE include nerve agents and pesticides, while reverse inhibitors such as donepezil and rivastigmine can be used to improve cognitive function in neurodegenerative diseases like Alzheimer’s. In immunohistochemistry, ACHE has positive membranous and secretory staining in the brain, endocrine tissues, immune tissues, muscle, gastrointestinal tissues and some positivity in reproductive tissues. References: BMJ. 1994 Apr 2; 308(6933): 868–869, PMID: 8173360; Front Neurosci. 2019 May 7;13:446, PMID: 31133787; Cell Tissue Res. 2006 Nov;326(2):655-69, PMID: 16802134;