Story-related and unmissable. Micolash, Host of the Nightmare is the boss that you will fight halfway up the Mergo's Loft area near the end of the game. This is more of a puzzle boss fight than a real boss fight, and you will spend most of your time chasing Micolash around rather than fighting him. He will summon marionnettes throughout this fight, and it is up to you whether or not you fight them. They are only a mild nuisance, so it is up to you.
To defeat Micolash, you have to chase him into a dead-end room, which will cause him to stop running away from you. Then simply attack him, staying to his side and back, since the only attack that he does that does any real damage to you is a frontal snake-grab attack. Dodge it to the side and you will be fine.
Once he is down to half health, he will teleport away and start running again. So chase him again, and he will eventually return to a dead-end room, but this time he will lock a door behind him. Go upstairs and fall through the floor to land in the room that he's in to continue fighting him. He has one new attack now, which is to send out a hail of homing missiles. These missiles don't do much damage, but they do momentarily stun you, so they are more of a nuisance than a threat. They are very difficult to dodge, but it is not a big deal if they hit you. See the following video guide: