Entire civilization flourished for 2000 years and then disappeared without any clue why. I have a pet theory about Indus Valley script - inscriptions on the seals are so short and unique because they are just name signatures, to stamp other objects. Having to be durable, they were the only inscribed objects that survived.
I think it's well understood that upliftment/desertification of the lower Indus valley resulted in many of the rivers the civilization was built around drying up.
Ancient DNA studies (Reich et. al) have shown a scattering of Indus peoples in all directions after that - including back to the southern Iranian plateau where they came from originally, and across the Indian subcontinent, forming a substratum of various populations across South and Central Asia.
They also reverted to smaller scale settlements, although with echoes of their previous material culture, eventually merging with later migrants and pre-existing indigenous populations.
After that, they very likely played a significant role in the second great urbanization of the Indian subcontinent [1], which took place in the first millennium BCE in the Gangetic plain, and also possibly in the parallel development of Iranian civilization. It is thought they were the original inventors of the famous Indo-Iranian oven known the tandoor, which seems to have remigrated back into South Asia long after the Indus people took it to Central Asia.
So while their original cities were abandoned, their influence was felt far and wide in the ancient world.
1. The first being the Indus Valley Civilization itself a few millenia earlier.